Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P＜0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P＜0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.

Objective To identify the risk factors of patients with frequent acute exacerbations of chro-nic obstructive pulmonary disease(AECOPD)and construct a prediction model based on the clinical data,provi-ding a theoretical basis for the clinical prevention and treatment.Methods A total of 25 638 COPD patients ad-mitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic(ROC)curve.Results In the patients with frequent AECOPD,male percentage(P＜0.001),age(P＜0.001),urban residence(P＜0.001),smoking(P＜0.001),length of stay(P＜0.001),total cost(P＜0.001),antibiotic cost(P＜0.001),diabetes(P=0.003),respiratory failure(P＜0.001),heart disease(P＜0.001),application of systemic glucocorticoids(P＜0.001),white blood cell count(P＜0.001),neutrophil percentage(P＜0.001),C-reactive protein(P＜0.001),total cholesterol(P＜0.001),and brain natriuretic peptide(BNP)(P＜0.001)were all higher than those in the patients with infre-quent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabe-tes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,re-spiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899(95％CI=0.892-0.905),the sensitivity of 85.30％,and the specificity of 79.80％.Conclusions Frequent AECOPD is associated with smoking,heart disease,ap-plication of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevat-ed BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide the-oretical support for the treatment and risk factor management of the patients.

The deubiquitinases (DUBs), as the crucial peptidohydrolases in the ubiquitin system, can reverse and strictly regulate ubiquitination and play key roles in various biological processes, including the regulation of protein stability, cell signal transduction. Ubiquitin-specific protease 28 (USP28) involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins, and is closely associated with the progression of colorectal, breast cancer, lung carcinomas, and pancreatic cancer. USP28 has been considered as a promising drug target in anticancer therapy, and the development of USP28 inhibitors has made some progress. In this article, we review the structure of USP28 and its interaction with substrates, discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.

Chronic kidney disease （CKD） is a global health problem， and its incidence increases year by year. Studies have revealed that the progression of CKD into end-stage renal disease （ESRD） is related to its inability to effectively eliminate toxins due to decreased renal function. Additionally， intestinal microflora produces a large amount of gut-derived uremic toxins （GDUTs） during protein fermentation. The theory of gut-kidney axis holds that gut and kidney interact with each other， and CKD reduces the ability to remove uremic toxins （UTs）， resulting in the accumulation of UTs in the blood. The accumulation of UTs also accelerates the deterioration of renal function， leading to a vicious circle. This paper focused on the sources of indoxyl sulfate and p-cresol sulfate in GDUTs and their mechanisms against CKD （such as inducing renal tubular cell death， oxidative stress and endothelial injury， promoting renal fibrosis and down-regulating renal protective protein） as well as the sources of trimethylamine oxide and its mechanisms against CKD （such as promoting renal fibrosis and inflammation）. Moreover， starting from gut-kidney axis， this paper summarized the ways of diet and nutrition regulation， toxin adsorption， enhanced dialysis to increase the clearance， inhibiting the sources of gut-derived toxins and traditional Chinese medicine （TCM） therapy （TCM preparations and TCM active ingredients） to regulate intestinal microecology and reduce the generation of GDUTs， aiming to provide new therapeutic ideas for delaying the progression of CKD.

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

OBJECTIVE To obser ve the efficacy and safety of rimazo lom for painless gastroscopy sedation in outpatients. METHODS Totally 84 patients who underwent painless gastroscopy were collected from the outpatient department of the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to June in 2021. By random number table method combined with envelope allocation concealment method ，they were randomly divided into observation group and control group ，with 42 cases in each group. The patients in the observation group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+Rimazole toluenesulfonate for injection 0.2 mg/kg. Patients in the control group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+ Propofol emulsion injection 2 mg/kg. Gastroscopy was performed after the patient ’s consciousness disappeared. The sedative efficiency，sedative onset time ，recovery time and the occurrence of adverse drug reaction were observed in 2 groups. The heart rate（HR），mean arterial pressure （MAP），pulse oxygen saturation （SpO2），modified observer ’s assessment of alertness/sedation （MOAA/S）score and Narcotrend score were recorded in 2 groups after entering the room （T0），after anesthesia induction （T1）， when gastroscope entered the throat （T2），at the end of gastroscope withdrawal （T3），5 min after gastroscopy （T4）. RESULTS There was no significant difference in the effective rate of sedation （100％），the incidence of respiratory depression ， nausea and vomiting between the two groups （P＞0.05）. The qq.com onset time of sedation in the observation group was longer than control group ，and the recovery time and the incidence ofhypotension，hypotension to be tre ated，injection pain and bradycardia in observation group were significantly shorter or lower than control group （P＜0.05）. At T 0，there was no significant difference in HR ，MAP，SpO2，MOAA/S score or Narcotrend score between two groups （P＞0.05）. From T 1 to T 4，the HR of control group was significantly lower than that of the same group at T 0，and significantly lower than observation group at the same time（P＜0.05）. From T 1 to T 3，the MAP of two groups were significantly lower than the same group at T 0（P＜0.05），but there were no significant differences between two groups and between T 4 and T 0（P＞0.05）. There was no significant difference in SpO 2 at different time points between two groups and HR at different time points in observation group （P＞0.05）. From T 1 to T 3，MOAA/S score and Narcotrend score of two groups were significantly lower than the same group at T 0，while the MOAA/S score and Narcotrend score at T 1 and T 3 and Narcotrend score at T 3 of observation group were significantly higher than control group at the same time （P＜0.05），and the Narcotrend score of observation group at T 2 was significantly lower than control group at the same time（P＜0.05）；at T 4，there were no significant differences in MOAA/S score and Narcotrend score between two groups （P＞ 0.05）. CONCLUSIONS Remazolam shows good sedative effect and safety for painless gastroscopy.

Objective: Whether metabolic redistribution occurs in patients with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is unknown. This study aimed 1) to propose a measure of the brain metabolic network for an individual patient and preliminarily apply it to identify impaired metabolic networks in patients with WMHs, and 2) to explore the clinical and imaging features of metabolic redistribution in patients with WMHs. Materials and Methods: This study included 50 patients with WMHs and 70 healthy controls (HCs) who underwent 18F-fluorodeoxyglucose-positron emission tomography/MRI. Various global property parameters according to graph theory and an individual parameter of brain metabolic network called “individual contribution index” were obtained. Parameter values were compared between the WMH and HC groups. The performance of the parameters in discriminating between the two groups was assessed using the area under the receiver operating characteristic curve (AUC). The correlation between the individual contribution index and Fazekas score was assessed, and the interaction between age and individual contribution index was determined. A generalized linear model was fitted with the individual contribution index as the dependent variable and the mean standardized uptake value (SUVmean) of nodes in the whole-brain network or seven classic functional networks as independent variables to determine their association. Results: The means ± standard deviations of the individual contribution index were (0.697 ± 10.9) x 10-3 and (0.0967 ± 0.0545) x 10-3 in the WMH and HC groups, respectively (p < 0.001). The AUC of the individual contribution index was 0.864 (95% confidence interval, 0.785–0.943). A positive correlation was identified between the individual contribution index and the Fazekas scores in patients with WMHs (r = 0.57, p < 0.001). Age and individual contribution index demonstrated a significant interaction effect on the Fazekas score. A significant direct association was observed between the individual contribution index and the SUVmean of the limbic network (p < 0.001). Conclusion The individual contribution index may demonstrate the redistribution of the brain metabolic network in patients with WMHs.

ObjectiveTo explore the carcinogenic mechanism of Campylobacter jejuni. MethodsEighteen female C57BL/6 Apc^Min/+ mice were randomly divided into the C. jejuni-infected group and the non-infection control group， each group with nine mice. Colorectal cancer of Apc^Min/+ mice was induced by dextran sulfate sodium and gavage of C. jejuni （or PBS as a control）. At the end of the experiment， the number of tumors in colorectal tissues of mice in each group was counted， and RNA was extracted from colorectal tumors， along with para-cancer tissues as controls. Transcriptome sequencing was performed by RNA-Seq technology， and data were analyzed for differentially expressed genes （DEGs）. Further， selected DEGs were subjected to GO （gene ontology） enrichment analysis and KEGG pathway enrichment analysis. ResultsCompared with that of the non-infection control group， the incidence of tumor in C. jejuni-infected group was significantly higher （P < 0.01）， which indicated the success of recreating the C. jejuni-induced CRC model. RNA-seq results showed that there were 394 and 501 DEGs （fold change > 4 and P < 0.05） in the C. jejuni-infected group compared with the two control groups， respectively. In GO enrichment analysis， DEGs were mainly enriched in immune response regulation and activation pathways， multiple protein transport pathways and receptor binding pathways. Cancer-related pathways and metabolic pathways were significant enriched in KEGG pathway enrichment analysis. Among these DEGs， 17 genes were found in comparisons with both control groups. The 17 genes were further selected， resulting in 14 “core” DEGs. In further validation of qRT-PCR， 9 genes were significantly differentially expressed， among which 3 genes were up-regulated （Gm1987， Saxo1 and Plekhs1） and 6 were down-regulated （Lrp2， Serpina3c， Fabp4， Tmem52， Lrrn4 and Upk3b）. ConclusionThis study emphasizes 9 host genes that may play important and unique roles in the occurrence and development of colorectal cancer induced by C. jejuni， which provides new insights for further studies on the carcinogenic mechanism of C. jejuni.

Liver disease is one of the major problems affecting human health. Ultrasound plays an important role in diagnosis and treatment of diffuse and focal liver diseases. However, conventional ultrasound evaluation is subjective and provides limited information. Artificial intelligence (AI) technology may supplement the disadvantages of conventional ultrasound and has been widely used in the field of ultrasound in liver diseases. To date, remarkable progress has been achieved for the use of AI technology in the diagnosis, assessment of therapeutic efficacy and prognosis prediction of liver diseases. This paper reviews the research progress of ultrasound image-based AI technology in the diagnosis and treatment of diffuse and focal liver diseases.